Tests to detect genetic mutations in urine can detect bladder cancer years before the disease shows clinical symptoms, new research presented at the European Association of Urology (EAU) Annual Congress in Milan, Italy has shown.
The study, conducted by researchers from France, Iran and the United Statesidentified mutations in ten genes capable of predicting the most common type of bladder cancer up to 12 years before diagnosis.
Bladder cancer is not a rare disease, as it is the fifth in the European Union, with more than 200,000 cases a year. Only about half of the people diagnosed with this advanced disease survive more than five years, mainly due to late diagnosis and disease recurrence. In contrast, if the cancer is detected at an early stage, more than 80% of patients survive at least five years.
The Florence Le Calvez-Kelm doctorate, principal investigator at the International Center for Research on Cancer (IARC) in Lyon, France, explains that “the diagnosis of bladder cancer is based on expensive and invasive procedures such as cystoscopy, which involves inserting a camera into the bladder. A simpler urinalysis that could accurately diagnose and even predict the likelihood of cancer years in advance could help detect more cancers at an early stage and avoid unnecessary cystoscopies in healthy patients,” he adds.
Mutations of 10 genes
The study was based on the UroAmp test, a general urinalysis that identifies mutations in 60 genes, developed by the Oregon Health Sciences University spin-off company Convergent Genomics. Building on previous research to identify gene mutations linked to bladder cancer, the research team narrowed the new test to focus on mutations in just ten genes.
In collaboration with colleagues from the Tehran University of Medical Sciences (Iran), tested the potential new test with samples from the Golestan cohort study, which has followed the health of more than 50,000 participants for ten years, all of whom provided urine samples at screening. Forty people in the study developed bladder cancer during that decade, and the team was able to analyze urine samples from twenty-nine of them, along with samples from another 98 similar participants as controls.
Of the 29 participants who had developed bladder cancer within the Golestan cohort, the test was able to accurately predict future bladder cancer in 19 (66%) of them, despite the fact that urine samples had been taken up to 12 years before clinical diagnosis.
Fourteen of these participants were diagnosed with bladder cancer within seven years of urine collection, and the test was able to predict cancer in 12 (86%) of them. The test was negative in 94 of the 98 participants (96%) who would not develop cancer in the future. Among those who tested negative but went on to develop bladder cancer, cancer was not diagnosed until at least six years after urine collection.
The test was also tested with colleagues from the Massachusetts General Hospital and The Ohio State University using samples from 70 bladder cancer patients and 96 controls, taken before cystoscopy. Unlike the Golestan study, some of these samples were provided by cancer patients on the day their disease was diagnosed, rather than many years before.
Mutations were found in the urine samples of 50 of the 70 patients (71%) whose tumors were visible during cystoscopy. In some cases it was a new diagnosis and in others a recurrent cancer. No mutations were found in 90 of the 96 (94%) patients with negative cystoscopy.
Until routine screening
Dr. Le Calvez-Kelm believes that these results demonstrate the potential of a genetic urine test for the early detection of bladder cancer. “We have clearly identified the most important acquired genetic mutations that can significantly increase the risk of developing cancer within 10 years,” she says. “Our results were consistent across two very different groups: people with known risk factors who underwent cystoscopy and those presumed to be healthy.
Should the results be replicated in larger cohorts, urine tests for these mutations could allow routine screening of high-risk groups, such as smokers or people exposed to known bladder carcinogens through their work. “, announces.
“This type of test could also be used when patients go to the doctor with blood in their urine, to help reduce the chances,” he says. unnecessary cystoscopies. If we can identify bladder cancer at an early stage, before the disease has progressed, we can save more lives.”
In the words of Dr. Joost Boormans, member of the EAU Scientific Congress Office and urologist at the Erasmus University Medical Center Rotterdam: “Investigation of this nature is very encouraging, as it shows that our ability to identify molecular alterations in liquid biopsies such as urine that could indicate the presence of cancer is constantly improving.
“Although we need to develop more accurate diagnoses, it is unlikely that we will have a mass screening program for bladder cancer. A urinalysis for genetic mutations could be useful in reducing the number of cystoscopies and examinations in patients with bladder cancer who are followed up for recurrence, as well as in those referred for blood in the urine. A simple urinalysis would be much easier for patients to perform than invasive procedures or scans, as well as being less expensive for healthcare services.”